PD is a movement disorder characterized by progressive degeneration of various neural structures, including parts of the basal ganglia and the cerebral cortex. In the United State, at least 500,000 people suffer from PD, with 50,000 new patients diagnosed each year. Worldwide, PD directly affects 4.1 million people. There are currently no treatments that cure, reverse, prevent, or slow the progression of PD.
Available treatments for PD currently include medication and deep brain stimulation (DBS), both of which mask the symptoms without changing the underlying pathology or pathophysiology. These treatment modalities each have significant limitations. Medication, which involves dopamine therapy (e.g., L-dopa), may be poorly tolerated due to its side effects, and its use can be limited by the short duration of action at later stages of disease. Furthermore, prolonged L-dopa use leads to disabling motor complications. Pharmacotherapy options besides L-dopa offer less potent symptom control and are often associated with undesirable side effects. At this stage, many patients undergo a DBS procedure which can help the motor complications as well as provide symptomatic relief beyond pharmacotherapy. However, in addition to risks inherent to invasive brain surgery, there are potential side effects, including speech impairment, worsening gait and balance, as well as cognitive and behavioral complications of DBS. As a result of limitations with these treatments, a novel approach to management of PD is needed: one that can extend the time period from medication to DBS horizon, or reduce the rate of increase in the reliance on medication.
An approach that has been attempted but produced puzzling results is transcranial direct current stimulation (tDCS). tDCS is a non-invasive procedure in which direct current (typically 1-2 mA) is passed through anode and cathode electrodes that are placed on the head and localized using MRI, transcranial magnetic stimulation (TMS), or EEG. A study examined patients in the moderate stage who were off medication for 12 hours and found that application of anodal tDCS over the left primary motor cortex (M1) produced 20% improvement of clinical motor scores (as compared to sham stimulation). This form of tDCS was found to reduce motor symptoms, but only in patients who were off their medication. Unfortunately, patients suffer when they are off their medication, so this result is interesting but only of limited clinical relevance.
A later double-blind study also applied anodal stimulation to the left M1 and measured the time it took for the patients to perform 10 elbow flexion movements and walk a fixed. In this study, the authors found that stimulation decreased walk time (the primary outcome) compared to sham, but only when tested off medication and after exclusion of an outlier. Furthermore, motor symptoms and time to perform the elbow task did not differ between sham and real stimulation.
However, it may be possible, if the technique is applied properly, that tDCS would lead to motor improvement in the medication ON state as well, which is more clinically relevant: (1) real life patients outside of experimental settings will be on medications; (2) if their maximum symptomatic benefits on optimized pharmacotherapy are still not satisfactory, only a treatment beyond what drugs can do will help.
Parkinson's disease is a progressive disease. Any symptom control treatment should be used for a long term and it should be independent to the disease stage. The treatment should not interfere with normal daily life of the patient and be applicable in any time even during the sleep time. It also should be very easy to use with minimum effort requirement from patient regarding electrode placement and stimulation parameter settings.
Accordingly, it would therefore be beneficial to improve motor symptoms in PD without having to take patients off of medication. It would also be beneficial to provide a device and system for long term use in the improvement of motor symptoms in PD and other movement disorders with brain stimulation therapy without the patient having to be involved in the device preparatory process and electrode placement. tDCS is a low cost, low risk procedure that if found effective, can be scaled to a large market, particularly in developing countries where costs and technology loom as barriers to adoption.